Contradictory data have been presented regarding the implication of the NACHT, LRR and PYD domains-containing protein 3 (NLRP3) inflammasome in age-related macular degeneration (AMD), the leading cause of vision loss in the Western world. Recognizing that antibody specificity may explain this discrepancy and in line with recent National Institutes of Health (NIH) guidelines requiring authentication of key biological resources, the specificity of anti-NLRP3 antibodies was assessed to elucidate whether non-immune RPE cells express NLRP3. Using validated resources, NLRP3 was not detected in human primary or human established RPE cell lines under multiple inflammasome-priming conditions, including purported NLRP3 stimuli in RPE such as DICER1 deletion and Alu RNA transfection. Furthermore, NLRP3 was below detection limits in ex vivo macular RPE from AMD patients, as well as in human induced pluripotent stem cell (hiPSC)-derived RPE from patients with overactive NLRP3 syndrome (Chronic infantile neurologic cutaneous and articulate, CINCA syndrome). Evidence presented in this study provides new data regarding the interpretation of published results reporting NLRP3 expression and upregulation in RPE and addresses the role that this inflammasome plays in AMD pathogenesis.

PURPOSE: The purpose of this article is to investigate the association between body mass index (BMI) and open-angle glaucoma (OAG) in a sample of the South Korean population. MATERIALS AND METHODS: The sample consisted of a cross-sectional, population-based sample of 10,978 participants, 40 years of age and older, enrolled in the 2008 to 2011 Korean National Health and Nutrition Examination Survey. All participants had measured intraocular pressure <22 mm Hg and open anterior chamber angles. OAG was defined using disc and visual field criteria established by the International Society for Geographical and Epidemiological Ophthalmology. Multivariable analyses were performed to determine the association between BMI and OAG. These analyses were also performed in a sex-stratified and age-stratified manner. RESULTS: After adjusting for potential confounding variables, lower BMI (<19 kg/m) was associated with greater risk of OAG compared with normal BMI (19 to 24.9 kg/m) [odds ratio (OR), 2.28; 95% confidence interval (CI), 1.22-4.26]. In sex-stratified analyses, low BMI remained adversely related to glaucoma in women (OR, 3.45; 95% CI, 1.42-8.38) but not in men (OR, 1.72; 95% CI, 0.71-4.20). In age-stratified analyses, lower BMI was adversely related to glaucoma among subjects 40- to 49-year old (OR, 5.16; 95% CI, 1.86-14.36) but differences in glaucoma prevalence were not statistically significant between those with low versus normal BMI in other age strata. CONCLUSIONS: Lower BMI was associated with increased odds of OAG in a sample of the South Korean population. Multivariate analysis revealed the association to be statistically significant in women and those in the youngest age stratum.

A 53-year-old man presented with smooth-domed, variegated cysts (polycystic disease) of all 4 eyelids, worse on the left side. Some of the cysts were clear, while others were creamy-white colored. In addition, multiple, very fine vesicopapules were noted along the eyelid margins. Histopathologic examination revealed a trichilemmal cyst, several pure apocrine hidrocystomas displaying multiple chambers, a hybrid cyst, and many small eccrine cysts of the deep dermis. The apocrine lesions, including the small ones at the eyelid margins, predominated. Smooth muscle actin sometimes positively stained outer myoepithelial cells in some of the apocrine cysts, which helped to distinguish them from eccrine cysts. Most noteworthy was the fact that the patient had been diagnosed with a prolactinoma 20 years earlier. There is only 1 previous report of multiple apocrine cysts and an antecedent prolactinoma in the dermatologic literature. This syndrome should be separated from that of Schöpf-Schulz-Passarge, which manifests multiple small eyelid apocrine cysts and other ectodermal dysplasias without any association with neoplasia, and from that of focal dermal hypoplasia (Goltz-Gorlin) syndrome with apocrine cysts but again without neoplasia.

Purpose: Precise measurements of visual fixation and its instability were recorded during optical coherence tomography (OCT) as a marker of neural network dysfunction in multiple sclerosis (MS), which could be used to monitor disease progression or response to treatment. Methods: A total of 16 MS patients and 26 normal subjects underwent 30 seconds of scanning laser ophthalmoscope (SLO)-based eye tracking during OCT scanning of retinal layer thickness. Study groups consisted of normal eyes, MS eyes without prior optic neuritis (MS wo ON), and MS eyes with prior optic neuritis (MS + ON). Kernel density estimation quantified fixation instability from the distribution of fixation points on the retina. In MS wo ON eyes, fixation instability was compared to other measures of visual and neurologic function. Results: Fixation instability was increased in MS wo ON eyes (0.062 deg2) compared to normal eyes (0.030 deg2, P = 0.015). A further increase was seen for MS + ON eyes (0.11 deg2) compared to MS wo ON (P = 0.04) and normal (P = 0.006) eyes. Fixation instability correlated weakly with ganglion cell layer (GCL) volume and showed no correlation with low-contrast letter acuity, EDSS score, or SDMT score. Conclusions: Fixation instability reflects the integrity of a widespread neural network germane to visual processing and ocular motor control, and is disturbed in MS. Further study of visual fixation, including the contribution of microsaccades to fixation instability, may provide insight into the localization of fixation abnormalities in MS and introduce innovative and easily measured outcomes for monitoring progression and treatment response.

PURPOSE: To evaluate the long-term alterations of corneal nerves in patients with herpes simplex virus (HSV) keratitis using in vivo confocal microscopy (IVCM). DESIGN: Prospective, longitudinal, cross sectional. METHODS: This study included 16 patients with a history of HSV keratitis and 15 age-matched normal controls. Slit-scanning IVCM was performed in all subjects at baseline and then after a mean follow-up of 37.3 ± 1.7 months in the patient group. Corneal subbasal nerve density and corneal sensation were compared between groups at baseline and follow-up. RESULTS: At baseline, the mean subbasal nerve density was significantly lower in both affected eyes (1.4 ± 0.6 mm/mm) and contralateral unaffected eyes (6.4 ± 0.7 mm/mm) compared with the controls (14.1 ± 1.6 mm/mm; all P  .001). At the end of follow-up, the mean nerve density in affected eyes increased to 2.8 ± 0.7 mm/mm (P = .006), with no significant change in contralateral unaffected eyes (6.5 ± 1.0 mm/mm, P = .72). However, both eyes had lower nerve density than controls (all P  .001). Corneal sensation was significantly lower in affected eyes (2.6 ± 0.6 cm) than in the control group (6.0 ± 0.0, P  .001) and showed no significant change at the end of follow-up (2.5 ± 0.6 cm, P = .80). Corneal sensation in contralateral unaffected eyes was not different in comparison with controls at both baseline and follow up (all p > .05). CONCLUSIONS: Our results demonstrate that although corneal nerve regeneration occurs in patients with HSV keratitis, this change is not clinically significant and does not results in changes of corneal sensation. Therefore, these patients need to be followed closely for complications of neurotrophic keratopathy and might benefit from neuro-regenerative therapies.

An infant presented with right upper eyelid ptosis and was subsequently diagnosed with acquired Horner syndrome. Further evaluation revealed a right-sided cervicothoracic lymphatic malformation. At 13 weeks of age, the child underwent percutaneous intracystic sclerotherapy with a mixture of sodium tetradecyl sulphate and ethanol. Twenty-one weeks after initial treatment, ophthalmic examination showed complete resolution of the blepharoptosis and pupillary miosis. Percutaneous sclerotherapy not only effectively treated the space-occupying lymphatic malformation but also reversed the Horner syndrome that was presumably induced by neural tension (more likely) or compression.

Importance: Anti-vascular endothelial growth factor (VEGF) therapies are a novel treatment option in retinopathy of prematurity (ROP). Data on dosing, efficacy, and safety are insufficient. Objective: To investigate lower doses of anti-VEGF therapy with ranibizumab, a substance with a significantly shorter systemic half-life than the standard treatment, bevacizumab. Design, Setting, and Participants: This randomized, multicenter, double-blind, investigator-initiated trial at 9 academic medical centers in Germany compared ranibizumab doses of 0.12 mg vs 0.20 mg in infants with bilateral aggressive posterior ROP; ROP stage 1 with plus disease, 2 with plus disease, or 3 with or without plus disease in zone I; or ROP stage 3 with plus disease in posterior zone II. Patients were recruited between September 2014 and August 2016. Twenty infants were screened and 19 were randomized. Interventions: All infants received 1 baseline ranibizumab injection per eye. Reinjections were allowed in case of ROP recurrence after at least 28 days. Main Outcomes and Measures: The primary end point was the number of infants who did not require rescue therapy at 24 weeks. Key secondary end points included time-to-event analyses, progression of physiologic vascularization, and plasma VEGF levels. Stages of ROP were photodocumented and reviewed by an expert committee. Results: Nineteen infants with ROP were enrolled (9 [47.4%] female; median [range] postmenstrual age at first treatment, 36.4 [34.7-39.7] weeks), 3 of whom died during the study (1 in the 0.12-mg group and 2 in the 0.20-mg group). Of the surviving infants, 8 (88.9%) (17 eyes [94.4%]) in the 0.12-mg group and 6 (85.7%) (13 eyes [92.9%]) in the 0.20-mg group did not require rescue therapy. Both ranibizumab doses were equally successful in controlling acute ROP (Cochran-Mantel-Haenszel analysis; odds ratio, 1.88; 95% CI, 0.26-13.49; P = .53). Physiologic intraretinal vascularization was superior in the 0.12-mg group. The VEGF plasma levels were not systematically altered in either group. Conclusions and Relevance: This pilot study demonstrates that ranibizumab is effective in controlling acute ROP and that 24% of the standard adult dose (0.12 mg) appears equally effective as 40% (0.20 mg). Superior vascularization of the peripheral retina with 0.12 mg of ranibizumab indicates that the lower dose may be favorable. Unchanged plasma VEGF levels point toward a limited systemic drug exposure after ranibizumab. Trial Registration: clinicaltrials.gov Identifier: NCT02134457 and clinicaltrialsregister.eu Identifier: 2013-002539-13.

Astrocytes make up approximately 30% of all the cells in the mammalian central nervous system. They are not passive, as once thought, but are integral to brain physiology and perform many functions that are important for normal neuronal development and metabolism, synapse formation, synaptic transmission, and in repair following injury/disease. Astrocytes also communicate with neurons, blood vessels, and other types of glial cells. Astrocytes within the optic nerve head region play a key role in glaucomatous axon degeneration. In this chapter, we describe ways in which astrocytes of the optic nerve head can be visualized, beginning with basic immunohistochemical staining methods, to single-cell dye injections and then to transgenic animals. We will also discuss the pros and cons of each method. Many of the methods were initially developed to visualize brain astrocytes; in some cases, the method has translated well to astrocytes of the optic nerve, and in others, it remains unclear.

Hearing loss, including genetic hearing loss, is one of the most common forms of sensory deficits in humans with limited options of treatment. Adeno-associated virus (AAV)-mediated gene transfer has been shown to recover auditory functions effectively in mouse models of genetic deafness when delivered at neonatal stages. However, the mouse cochlea is still developing at those time points, whereas in humans, the newborn inner ears are already fully mature. For effective gene therapy to treat genetic deafness, it is necessary to determine whether AAV-mediated therapy can be equally effective in the fully mature mouse inner ear without causing damage to the inner ear. This study tested several AAV serotypes by canalostomy in adult mice. It is shown that most AAVs transduce the sensory inner hair cells efficiently, but are less efficient at transducing outer hair cells. A subset of AAVs also transduces non-sensory cochlear cell types. Neither the surgical procedure of canalostomy nor the AAV serotypes damage hair cells or impair normal hearing. The studies indicate that canalostomy can be a viable route for safe and efficient gene delivery, and they expand the repertoire of AAVs to target diverse cell types in the adult inner ear.